RESUMEN
Mucin O-glycosylation is characterized in cancer by aberrant expression of immature carbohydrate structures (Tn, T, and sialyl-Tn antigens). The UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-T) family enzymes regulate the initial steps of mucin O-glycosylation and could be responsible for the altered glycosylation observed in cancer. Considering that we recently found the ppGalNAc-T6 mRNA expressed in breast carcinomas, we produced a highly specific monoclonal antibody (MAb T6.3) to assess the expression profile of ppGalNAc-T6 protein product in breast tissues. The expression of ppGalNAc-T6 by breast carcinoma cells was confirmed on MCF-7 and T47D cell lines. In formalin-fixed tissues, ppGalNAc-T6 expression was observed in 60/74 (81%) breast cancers, 21/23 (91.3%) adjacent ductal carcinoma in situ (DCIS), 4/20 benign breast lesions (2/2 sclerosing adenosis and 2/13 fibroadenoma), and in 0/5 normal breast samples. We observed a statistically significant association of ppGalNAc-T6 expression with T1 tumor stage. This fact, as well as the observation that ppGalNAc-T6 was strongly expressed in sclerosing adenosis and in most DCIS, suggests that ppGalNAc-T6 expression could be an early event during human breast carcinogenesis. Considering that an abnormal O-glycosylation greatly contributes to the phenotype and biology of breast cancer cells, ppGalNAc-T6 expression could provide new insights about breast cancer glycobiology.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/enzimología , N-Acetilgalactosaminiltransferasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Monoclonales , Enfermedades de la Mama/enzimología , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/enzimología , Carcinoma Lobular/enzimología , Carcinoma Papilar/enzimología , Femenino , Humanos , Inmunohistoquímica , Glándulas Mamarias Humanas/enzimología , Metaplasia , Ratones , Persona de Mediana Edad , N-Acetilgalactosaminiltransferasas/inmunologíaRESUMEN
Tyrosine protein kinase (TPK) activity is associated to malignant cellular transformation. This work compares TPK activity in 27 surgical biopsy samples of mammary carcinoma, 10 samples of normal mammary tissue. TPK activity was determined in tissue homogenates using (Val5) angiotensin II as exogenous substrate. In samples of mammary carcinoma, TPK activity was 33.86 ñ 31.98 pmol P32/mg protein/30 min. This value was significantly higher that those observed in fibrocystic disease (3.92 ñ 2.35), fibroadenomas (13.86 ñ 10.9) and normal tissue (3.56 ñ 3.02)